Recently identified lipids have been shown to exhibit phagocyte modulating effects formerly attributed only to peptides. The proposed research is designed to answer several basic questions regarding the effects of lipids on phagocyte functions including chemotaxis, phagocytosis, locomotion, and lysosomal enzyme release. The endogenous chemotactic lipid, HETE (12L-OH, 5,8,10,14-eicosatetraenoic acid) and its parent compound arachidonic acid will be used as a prototype in studies of structure vs. function. Analogs and sub-analogs of HETE will be synthesized chemically and enzymatically in order to determine the minimum structural requirements for chemotactic function. Metabolism of lipid modulators will be monitored by recovering lipid breakdown products from lipid-cell incubations. Product identification will be made using thin layer chromatography, spectrophotometry, high pressure liquid chromatography, and mass spectrometry. Chemotaxis and locomotion will be assayed using Zigmond's leading front technique and Boyden's micropore filter method. Phagocytosis will be measured by the uptake of opsonized microorganisms or collodial gold particles. In light of the current knowledge of peptide-mediated phagocyte responses, information gained from this project should allow a broader perspective for rationalizing the mechanisms by which phagocytes perform their host defense functions.